Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer

• Published in: Annals of oncology Vol. 14; no. 6; pp. 849 - 855
• Main Authors: Xenidis, N., Vlachonikolis, I., Mavroudis, D., Perraki, M., Stathopoulou, A., Malamos, N., Kouroussis, C., Kakolyris, S., Apostolaki, S., Vardakis, N., Lianidou, E., Georgoulias, V.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-06-2003
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; blood; breast cancer; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Chemotherapy, Adjuvant; CK-19 mRNA; Disease-Free Survival; DNA Primers - chemistry; Female; Follow-Up Studies; Gynecology. Andrology. Obstetrics; Humans; Keratins - genetics; Key words: adjuvant chemotherapy; Mammary gland diseases; Medical sciences; Middle Aged; Neoplastic Cells, Circulating; Predictive Value of Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - blood; RNA, Neoplasm - blood; Sensitivity and Specificity; Survival Rate; Tumors; Antineoplastic agent; Cytokeratin; Biological fluid; Residual tumor; adjuvant chemotherapy; Prognosis; Adjuvant treatment; Biological marker; Blood; Surgery; Female; Mammary gland; Tumor cell; Human; Postoperative; Drug combination; breast cancer; Cytokeratin 19; Malignant tumor; Gene expression; CK-19 mRNA; Mammary gland diseases; Chemotherapy; Treatment; Predictive factor
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdg259

Background: The purpose of this study was to evaluate the prognostic significance of the molecular detection of cytokeratin 19 (CK-19) mRNA-positive cells in the peripheral blood of women with operable breast cancer after the completion of adjuvant chemotherapy. Patients and methods: Blood from 161 patients with stage I and II breast cancer, obtained after the completion of adjuvant chemotherapy, was tested by nested RT–PCR for CK-19 mRNA detection. Using univariate and multivariate analyses possible interactions with other prognostic factors and association of CK-19 mRNA detection with risk of relapse, disease-free interval (DFI) and overall survival were investigated. Results: After completion of adjuvant chemotherapy, 27.3% of patients had peripheral blood CK-19 mRNA-positive cells; there was no association of this finding with any other prognostic factors or the type of chemotherapy regimen used. For patients with less than four involved axillary lymph nodes the risk of relapse was 3.81 [95% confidence interval (CI) 1.06–13.71] times higher, and the DFI was significantly reduced (P = 0.028) if CK-19 mRNA-positive cells were detectable in the blood after the completion of adjuvant chemotherapy. In contrast, for patients with four or more involved lymph nodes, the presence of CK-19 mRNA-positive cells after adjuvant chemotherapy did not significantly affect the risk of relapse or DFI. Furthermore, the risk of relapse was higher (hazards ratio 3.70; 95% CI 1.09–13.89) and the DFI was reduced (P = 0.022) for patients with detectable CK-19 mRNA-positive cells following adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as compared with epirubicin, cyclophosphamide and 5-fluorouracil (FEC) or sequential taxotere–epirubicin and cyclophosphamide (T/EC) chemotherapy. Conclusions: The detection of CK-19 mRNA-positive cells in the peripheral blood after adjuvant chemotherapy may be of clinical relevance for patients with early breast cancer and less than four involved axillary lymph nodes.